The long-term goal of this project is to develop a minimally invasive, effective, and safe treatment for prostate cancer. Our specific aims are to 1) to optimize transurethral high intensity ultrasonic applicators for prostate ablation, 2) to rigorously evaluate the applicators in a canine model, including study of the accuracy of MR-guidance of ablation and elucidation of longer-term (6 weeks) fate of insonated prostate 3) to evaluate the relative advantages and differences of MR-guided transurethral high- intensity ultrasound compared to transrectal HIFU for targeted prostate ablation, 4) to evaluate the ability of our applicators to locally ablate selected prostate tissues under MRI guidance in human subjects with demonstrated patient safety. In the US, prostate cancer is the most common malignancy in men, excluding skin cancer. The techniques we are currently developing are designed for local control of prostate cancer (i.e., control of the primary process itself by ablation of prostatic tissues), and since up to 88% of prostate cancers are currently presenting as organ-confined disease, these therapies would thus be applicable to the majority of newly presenting cases. Focused ultrasound is a promising technique for the next generation of non- invasive cancer therapy systems. With this technology, ultrasound energy is focused at a point deep within the body to thermally ablate targeted tissue. This can be done with minimal heat deposition from the skin or cavity surface, without puncture or incision. The effort proposed here addresses the main technical challenges to using transurethral focused ultrasound therapy. The applicators will be developed to couple focused ultrasound treatment with Magnetic Resonance image guidance to allow precise targeting of the thermal energy to target tissues. Techniques to monitor heat deposition in targeted regions of the prostate gland, through accurate temperature mapping will be developed to insure that the entire target volume is being treated, and to ascertain that critical structures such as the rectum, the neurovascular bundles, and the urethra remain sufficiently cool to avoid damage. The new applicators and systems will be developed and evaluated both in vitro and in vivo. PUBLIC HEALTH RELEVANCE: We will develop and test an integrated system for the controlled ablation of prostate cancer using transurethral devices delivering high-intensity ultrasound to the prostate, directed by MRI thermal imaging, and incorporating rectal and urethral cooling